June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Safety and efficacy of a novel injectable anti-TNF-α/anti-VEGF drug delivery system for corneal and retinal protection after injury.
Author Affiliations & Notes
  • Chengxin Zhou
    Boston Keratoprosthesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
    Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Pui-Chuen Hui
    Boston Keratoprosthesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
    Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Natalie Wolkow
    David G. Cogan Laboratory of Eye Pathology and Ophthalmic Plastic Surgery Service, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
    Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Claes H Dohlman
    Boston Keratoprosthesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
    Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Demetrios G. Vavvas
    Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
    Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Eleftherios I Paschalis
    Boston Keratoprosthesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
    Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Chengxin Zhou, None; Pui-Chuen Hui, None; Natalie Wolkow, None; Claes Dohlman, None; Demetrios Vavvas, None; Eleftherios Paschalis, None
  • Footnotes
    Support  Boston Keratoprosthesis Fund at Massachusetts Eye and Ear
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 1206. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Chengxin Zhou, Pui-Chuen Hui, Natalie Wolkow, Claes H Dohlman, Demetrios G. Vavvas, Eleftherios I Paschalis; Safety and efficacy of a novel injectable anti-TNF-α/anti-VEGF drug delivery system for corneal and retinal protection after injury.. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1206.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : To develop a novel therapy to suppress acute and long-term ocular complications after injury by using an injectable thermosensitive drug delivery system (DDS) for sustained subconjunctival delivery of anti-TNF-α and anti-VEGF reagents.

Methods : A thermosensitive, biodegradable hydrogel DDS (PLGA-PEG-PLGA triblock) loaded with 2mg of infliximab and aflibercept (1:2; Infli/Afli) was injected subconjunctivally in 3 Dutch-belted rabbits after corneal alkali injury. Control rabbits received human IgG loaded DDS (n=4) or only aflibercept DDS (n=3). Animals were followed for 3 months and assessed in vivo for tolerability, corneal neovascularization (CoNV), re-epithelialization, and ex vivo for retinal ganglion cell (RGC) loss, optic nerve axon loss, and expression of inflammatory markers. Drug release kinetics was assessed in-vitro by using fluorescein-dextran as a model drug, and in-vivo by aqueous humor analysis.

Results : Infli/Afli DDS treatment led to complete suppression of CoNV for over 3 months without adverse effects or reactions by the eye, while aflibercept DDS showed mild CoNV (~10% of cornea) and IgG DDS significantly more CoNV (~ 30% of cornea). Eyes treated with Infli/Afli DDS showed minimal corneal epithelial defect (0-2% of cornea) over 3 months, while IgG DDS treated eyes exhibited epithelial defect up to 11% of the cornea area albeit wound closure at 3 months. Aflibercept DDS group exhibited persistent corneal epithelial defects (~7% at 3 months). Histologically, Infli/Afli DDS reduced CD45+ immune cell accumulation (92%, P<0.05) and ameliorated TNF-α expression (70%, P<0.05) in the cornea, as compared to IgG DDS. Subconjunctival administration of infli/afli DDS achieved sustained retinal drug diffusion, and prevented RGC loss as compared to the other two groups at 3 months which exhibited 33-63% RGC loss. Quantification of IgG content in the aqueous humor using ELISA assay demonstrated that the DDS provided sustained, first-order drug release for over 3 months.

Conclusions : Sustained subconjunctival administration of infliximab and aflibercept using a thermosensitive biodegradable DDS that targets TNF-α and VEGF signaling pathways is an extremely effective therapy for preventing post-injury corneal inflammation and neovascularization, while providing the much needed retinal protection against RGC loss. Further studies are warranted.

This is a 2021 ARVO Annual Meeting abstract.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×